Currently 30 million Americans with elevated cholesterol receive statin therapy, making statins the most prescribed drug class in the U.S. Statin Induction and Neuro-Myopathy (SINM), the balance of potency and safety, is the main clinical management challenge of these drugs, particularly when treatment targets are aggressive requiring LDL cholesterol levels below 100 mg/dl. In medical practice, Neuro-Myopathy presents as a constellation of neuromuscular side effects, including myalgia (muscle aches, cramps, weakness) and myopathy (muscular injury monitored by serum creatine kinase (CK) elevation). Neuro-myopathy is more frequent at the higher doses required for treating advanced cardiovascular disease and varies in extent between individual statins and from patient to patient. Statin usage is ultimately limited by toxicity. Clearly there is an urgent need to simultaneously avert side effects and optimize lipid lowering at the outset of treatment to bolster success in lowering cardiovascular disease risk in literally millions of patients. Recognizing that clinicians balance safety with efficacy when prescribing statins, our research group and others have established genetic markers that are valid candidates for a panel of safety and efficacy markers. The SINM PhyzioType System is the first diagnostic tool to integrate statin safety and efficacy markers for clinical use. The SINM PhyzioType system can predict the safety and efficacy of the pre-eminent statin drugs (namely, atorvastatin [Lipitor(R)], simvastatin [Zocor(R)], and rosuvastatin [Crestor(R)]-which together account for 85% of the U.S. market share8) according to the genome of each patient, enabling selection of the optimal drug for each patient. Alternatively if a patient's genomic profile proves to be incompatible with statins, the clinician can opt to prescribe another drug class. This Phase II Renewal Program is entitled SYSTEM FOR DNA-GUIDED OPTIMIZATION AND PERSONALIZATION OF STATIN THERAPY. Our previous Fast-Track SBIR Program enabled the discovery of gene markers and configuration of predictive bioclinical algorithms, and it advanced the clinical development of the SINM PhyzioType product closer to commercialization. The proposed Phase II Renewal Program will validate the performance of the SINM PhyzioType product in a prospective study of an independent population of 400 patients naove to statin therapy or who had not received statins for at least 3 months. Allocated funds will be used to validate the product for personalized clinical management of statins, to develop a medical informatics interface enabling use of the product by clinicians (Personalized Health Portal) and to prepare the SINM PhyzioType for commercialization. With this project, Genomas will continue to enlist some of the most highly qualified lipid clinical specialists in the world, including Paul D. Thompson, M.D., of Hartford Hospital's Division of Cardiology, John P. Kane, M.D., of the Cardiovascular Research Institute at University of California at San Francisco, and Bruce Gordon, M.D., of the Rogosin Institute at New York Presbyterian Medical Center for this Program. Theodore Holford, Ph.D., of the Yale School of Medicine will serve as a consultant in biostatistics. The expected outcome is final development of the Genomas product SINM PhyzioTypeTM System, that predicts the variable lipid-altering efficacy and the risk of drug-induced neuromuscular side effects that arise in the substantial segment of patients receiving statins. With data collected Phase II Renewal funding, Genomas will be able to serve confirmatory proof that the PhyzioType product is a reliable, reproducible and cost-effective product enabling physicians to optimize treatment strategies in lipid disorders while avoiding neuromyopathy. The goal is to enable clinicians to deploy a genetic decision support system to manage statins, prescribe these drugs on a DNA-guided, personalized basis and effectively lower the risk of cardiovascular disease for each patient. PUBLIC HEALTH RELEVANCE: In the proposed Phase II Renewal Program, the SINM PhyzioTypeTM System for optimization and personalization of statin therapy will be validated through a prospective study to finalize the product ahead of commercialization. This validation study will serve confirmatory proof that the SINM PhyzioTypeTM System is a reliable, reproducible and cost-effect product enabling physicians to optimize treatment strategies in lipid disorders and minimize detrimental neuromuscular side effects. This pioneering product, which represents the first tool to integrate statin safety and efficacy markers for clinical use, will advance the practice of personalized medicine and reduce side effects while elevating therapeutic benefits of the country's most popular drugs that are already on the market.